Background

Type 2 diabetes mellitus (T2DM) is an important risk factor for macro-and microvascular complications, such as the development of chronic kidney disease (CKD). Moreover, CDK can further increase adverse CV outcomes [1,2]. It is therefore crucial to reduce CV risk by managing glycaemic control in T2DM patients. Glucose-lowering therapy in combination with managing multiple CV risk factors, has been previously been shown to lead to a reduction of adverse CV outcomes in T2DM patients [3,4].

Sitagliptin, a recently developed dipeptidyl peptidase 4 inhibitor (DPP-4i), improves glycaemic control in T2DM patients and its CV safety was investigated with the TECOS trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). In this trial, 14,671 patients with T2DM and documented CV disease where randomised to sitagliptin or placebo, on top of standard therapies [5]. Results showed that sitagliptin did neither increase nor decrease CV events, heart failure hospitalisation, or adverse events in general.

In this post hoc analysis of the TECOS trial, the CV and CKD outcomes were evaluated in light of the estimated glomerular filtration rate (eGFR).

eGFR data was available for 14,525 patients, who were categorised into eGFR stages 1, 2, 3a, and 3b (≥90, 60–89, 45–59, or 30–44 mL/min/1.73 m2, respectively). Baseline urinary albumin to creatinine ratios (UACR) were available for 5,148 patients. Median follow-up was 3 years.

Main results

22.9% of participants were categorised as eGFR stage 1, 54.2% as stage 2, 17.5% as stage 3a and 5.4% as stage 3b.

The mean eGFR reduction over 4 years from baseline was greater in the sitagliptin group than in the placebo group (-4.0 ± 18.4 vs. -2.8 ± 18.3 mL/min/1.73 m2). Although the median eGFR was marginally lower in the sitagliptin group compared to placebo (mean difference -1.34, P<0.0001), which remained consistent over time, the 4-year between-treatment group differences were similar for each eGFR stage, with no significant interactions of treatment effect by eGFR stage (P interaction = 0.14).

Also mean UACR was consistently lower in the sitagliptin group compared to placebo (mean difference -0.18, P=0.031), but the 4-year UACR between-treatment group differences were similar (P interaction = 0.68).

Conclusion

This post hoc analysis of the TECOS trial demonstrated that although reduced eGFR and increased UACR were associated with a significantly increased risk of CV events, sitagliptin had, irrespective of baseline eGFR, no clinically significant impact on CV or CKD outcomes.